Direct contact between human peripheral blood mononuclear cells and renal fibroblasts facilitates the expression of monocyte chemoattractant protein-1
Direct contact between human peripheral blood mononuclear cells and renal fibroblasts facilitates the expression of monocyte chemoattractant protein-1
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DOI：
10.1159/000071480
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发表时间：
2003-07-01
影响因子：
4.2
通讯作者：
Suzuki, H
中科院分区：
文献类型：
--
作者：
Hao, LR;Okada, H;Suzuki, H
背景细胞间相互作用被认为是多种生物过程的重要特征。在促炎过程中，系膜细胞与单核/巨噬细胞的相互作用诱导单核细胞趋化蛋白-1（MCP-1）的表达，这可能在肾小球肾炎中发挥作用。在这项研究中，我们研究了免疫细胞和肾成纤维细胞之间的细胞间相互作用是否诱导MCP-1基因表达，这可能涉及肾间质炎症。研究方法：使用人肾成纤维细胞系tNKF（来自正常肾脏）和tFKIF（来自纤维化肾脏）以及外周血单核细胞（PBMC）来评估细胞间接触对成纤维细胞中MCP-1 mRNA表达的影响。在用肿瘤坏死因子-α（TNF-α）和来自PBMC的培养上清液刺激后，还检查了成纤维细胞中MCP-1基因的表达。RT-PCR检测MCP-1 mRNA表达。细胞间粘附分子-1（ICAM-1）和血管内皮粘附分子-1（VCAM-1）的中和抗体用于阻断成纤维细胞与PBMC之间的细胞-细胞接触。结果：TNF-α和PBMC培养上清可增加tNKF细胞MCP-1基因的表达。与PBMC接触培养也显著增加tNKF细胞中MCP-1基因的表达。尽管tFKIF中MCP-1 mRNA的基础水平高于tNKF细胞，但tFKIF细胞对本研究中的任何刺激均无显著反应。用抗ICAM-1抗体预处理后，tNKF细胞中MCP-1基因表达在与PBMC接触培养中被显著抑制。抗VCAM-1抗体治疗没有效果。结论：结果表明，肾成纤维细胞与PBMC之间的相互作用是通过直接接触和分泌的体液因子介导的。肾成纤维细胞上的ICAM-1可能参与了直接的细胞间相互作用，诱导MCP-1基因表达，这似乎参与了肾间质炎症。版权所有（C）2003 S. Karger AG，巴塞尔。
Background. Cell-to-cell interaction is thought to be an important feature of a variety of biological processes. As far as the proinflammatory process is concerned, the interaction between mesangial cells and monocytes/macrophages induces the expression of monocyte chemoattractant protein-1 (MCP-1), and this may play a role in glomerulonephritis. In this study, we investigated whether the cell-to-cell interaction between immune cells and renal fibroblasts induces MCP-1 gene expression, which may be involved in interstitial inflammation in the kidney. Methods: Human renal fibroblast cell lines, tNKF (from a normal kidney) and tFKIF (from a kidney with fibrosis), and peripheral blood mononuclear cells (PBMC) were used to assess the effect of cell-to-cell contact on the expression of MCP-1 mRNA in the fibroblasts. The expression of the MCP-1 gene in the fibroblasts was also examined after stimulation with tumor necrosis factor-alpha (TNF-alpha) and the culture supernatant from PBMC. RT-PCR was used to detect MCP-1 mRNA expression. Neutralizing antibodies to intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial adhesion molecule-1 (VCAM-1) were used to block the cell-to-cell contact between the fibroblasts and PBMC. Results: TNF-alpha and the culture supernatant from PBMC increased MCP-1 gene expression in tNKF cells. Contact culture with PBMC also significantly increased MCP-1 gene expression in tNKF cells. Although the basal level of MCP-1 mRNA was higher in tFKIF than tNKF cells, tFKIF cells did not respond significantly to any stimulation in this study. Following pretreatment with anti-ICAM-1 antibody, MCP-1 gene expression in tNKF cells was significantly suppressed in contact culture with PBMC. Anti-VCAM-1 antibody treatment had no effects. Conclusion: It is suggested that the interaction between renal fibroblasts and PBMC was mediated through direct contact and by secreted humoral factors. ICAM-1 on renal fibroblasts may be involved in the direct cell-to-cell interaction inducing MCP-1 gene expression, which seems to be involved in renal interstitial inflammation. Copyright (C) 2003 S. Karger AG, Basel.